Brain Damage from HIV, Alzheimer's May Involve Inflammation

Both HIV and Alzheimer's disease can damage the brain, but most people think the similarity between the two ends there. Recent research from San Francisco Veterans Affairs Medical Center (SFVAMC) suggests a closer connection -- the brain damage from both diseases appears to involve inflammation, suggesting that anti-inflammatory drugs could help.

The latest findings to support this link show that AIDS dementia, like Alzheimer's, may now be a chronic condition. The study, published in the latest issue of the journal AIDS, shows that immune cell markers of AIDS dementia remain even after a patient is treated with anti-retroviral drug cocktails.

These same markers are elevated in patients with Alzheimer's disease, said lead author Lynn Pulliam, chief of microbiology at SFVAMC and UCSF professor of laboratory medicine and medicine.

"The brain wages an immune response against HIV infection. We believe that the brain is damaged by inflammatory toxins that are released as part of the brain's immune response. The amyloid plaques of Alzheimer's are also believed to cause a toxic inflammatory response," Pulliam said.

Certain anti-inflammatory drugs may be able to reduce the damage from these toxins, according to cell culture studies published earlier this year in the journal Brain Research by Pulliam's group. The brains of AIDS dementia patients have increased numbers of immune cells called monocyte/macrophages, which secrete chemicals that are toxic to cultured brain cells. The study found that treatment with an experimental anti-inflammatory drug developed by Centaur Pharmaceuticals prevented this toxicity.

The same drug, called CPI-1189, has been tested on patients with AIDS dementia in preliminary Phase II clinical trials, and it appears to improve patients' performances on tests of psychomotor and cognitive function, according to Centaur Pharmaceuticals.

"It would be very exciting if anti-inflammatory drugs turn out to be an effective additional treatment for AIDS dementia, or for Alzheimer's disease, because it would be a relatively simple approach that we already understand to some degree," Pulliam said.

Recent research from other investigators has suggested that non-steroidal anti-inflammatory drugs, such as ibuprofin, may help to delay the onset of Alzheimer's disease, further supporting the importance of inflammation in both AIDS dementia and Alzheimer's, Pulliam said.

The new study from Pulliam's group focuses on a subset of monocyte/macrophages that are more numerous in both AIDS dementia and in Alzheimer's disease.

Monocyte/macrophages that display a surface molecule called CD69 are much more prolific in the blood of AIDS dementia patients and patients with Alzheimer's disease than in healthy people.

The study found that after AIDS dementia patients were treated with a complete anti-AIDS drug regimen, their levels of CD69 cells were somewhat lower but still higher than non-demented AIDS patients and similar to those of patients with Alzheimer's disease.

"It appears that HIV-associated dementia has evolved into a more protracted disorder. Although treatment with anti-retroviral drugs appears to cause macrophages monocyte/macrophages to secrete lower levels of toxins, a more subtle neurotoxicity continues to disable neurons," Pulliam said.

This neurotoxicity appears to alter levels of important structural and functional proteins in the brain, she said.

Co-authors on the paper in AIDS included Leonard Kusdra, staff research associate; and Dr. Dawn McGuire, UCSF assistant clinical professor of neurology and medicine.

This study was supported by a grant from the National Institute of Mental Health.

The San Francisco Veterans Affairs Medical Center has been a primary affiliate of University of California, San Francisco since 1974. The UCSF School of Medicine and the SFVAMC collaborate to provide education and training programs for medical students and residents at SFVAMC. SFVAMC maintains full responsibility for patient care and facility management of the medical center. Physicians at SFVAMC are employed by the Department of Veterans Affairs and also hold UCSF faculty appointments.